Adrenal carcinoma

Jump to: navigation, search

For patient information, click here

Adrenal carcinoma Microchapters

Patient Information

Overview

Historical Perspective

Classification

Adrenocortical carcinoma
Sex cord-Stromal Tumor
Adenomatoid tumor
Adrenolipoma
Schwannoma
Hematological malignancy
Pheochromocytoma
Paraganglioma
Neuroblastoma
Ganglioneuroma

Pathophysiology

Epidemiology and Demographics

Risk factors

Natural History, Complications and Prognosis

Diagnosis

Treatment

Differentiating Adrenal carcinoma from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sara Mohsin, M.B.B.S.[2]

Synonyms and Keywords: Adrenocortical carcinoma, Adrenal cortical carcinoma, Adrenal cortical cancer, Adrenal cortex cancer, Adrenal cancer, Adrenal tumor, Neuroblastoma, Pheochromocytoma, Ganglioneuroma, Adrenocortical adenoma, Adenomatoid tumor, Myelolipoma, Schwannoma.

Overview

Adrenal carcinoma or adrenal tumor is an aggressive disease which can originate either in the cortex (steroid hormone-producing tissue) or medulla of the adrenal gland. According to the 2017 WHO classification of adrenal tumors, adrenal cortical tumors are subclassified into cortical adenoma, cortical carcinoma, sex cord stromal tumors, adenomatoid tumor, mesenchymal and stromal tumors (myelolipoma, schwannoma), hematological tumors and secondary tumors, whereas tumors of adrenal medulla are subclassified into pheochromocytoma, paraganglioma, neuroblastic tumors, composite pheochromocytoma, and composite paraganglioma. Pathogenesis includes many genetic pathways, most prominent being Wnt-Beta catenin pathway and also association with other diseases such as multiple endocrine neoplasia (MEN1 and MEN2), familial adenomatous polyposis, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Lynch syndrome,von Hippel-Lindau disease, carney Complex/Syndrome, neurofibromatosis type 1 and congenital adrenal hyperplasia. Adrenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients with steroid hormone-producing ("functional") tumors, including Cushing's syndrome, Conn syndrome, virilization, and feminization. Adrenal carcinoma can be treated with both medical therapy and surgery depending upon the stage of the tumor.

Historical perspective

Classification

Updated 2017 WHO classification of adrenal tumors
Tumors of adrenal gland
Tumors of adrenal cortex
Tumors of the adrenal medulla

and extra-adrenal paraganglia

Pathophysiology

Normal anatomy and physiology of adrenal glands

Normal anatomy and function of Adrenal glands
Adrenal gland layers Functions
Adrenal cortex (outer layer)
Adrenal medulla (Inner layer)
source: By David Richfield (User:Slashme) and Mikael Häggström. Derived from previous version by Hoffmeier and Settersr.In external use, this diagram may be cited as:Häggström M, Richfield D (2014). "Diagram of the pathways of human steroidogenesis". Wikiversity Journal of Medicine 1 (1). DOI:10.15347/wjm/2014.005. ISSN 20018762. - Self-made using bkchem and inkscape, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6355511

Epigenetics

VEGF signaling, source: By Mikael Häggström.When using this image in external works, it may be cited as:Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.orBy Mikael Häggström, used with permission. - [1]Interactions of VEGF ligands and VEGF receptors ResearchVEGF.com, retrieved on November, 13, 2009, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3475250
WNT pathwayssource: By Fred the OysteriThe source code of this SVG is valid.This vector graphics image was created with Adobe Illustrator., GFDL, https://commons.wikimedia.org/w/index.php?curid=36340188
microRNA function, source: By Kelvinsong - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=23311105

Gross pathology

Adrenocortical carcinoma

A large adrenal cortical carcinoma resected from a 27-year-old woman. The tumor measured 17 cm in diameter and invaded kidney and spleen which necessitated en bloc removal of these organs with the tumor. - By AFIP Atlas of Tumor Pathology - [1], Domena publiczna, https://commons.wikimedia.org/w/index.php?curid=6719487

Pheochromocytoma

Bilateral pheochromocytoma in MEN2. Gross image. Source: https://upload.wikimedia.org/wikipedia/commons/5/5f/Bilateral_pheo_MEN2.jpg

Microscopic pathology

Pathologic criterias for adrenocortical carcinoma

Pathologic criteria Details Age applicability
Weiss criteria

Adrenocortical carcinoma can be diagnosed by the presence of at least 3 of the 9 Weiss criteria:

  1. High nuclear grade (III or IV)
  2. High mitotic rate i.e. presence of >5 mitotic figures/50 high-power fields, definition suffers from HPFitis (counting 10 random fields in area of greatest number of mitotic figures on 5 slides with the greatest number of mitosis)
  3. Atypical mitoses (abnormal distribution of chromosomes or excessive number of mitotic spindles)
  4. Cleared or vacuolated cytoplasm in >/= 25% of the tumor cells
  5. Sheeting (diffuse architecture of patternless sheets of cells)) in >= 1/3 of tumor cells
  6. Necrosis in nests (microscopic necrosis)
  7. Venous invasion (veins must have smooth muscles in wall; tumor cell clusters or sheets forming polypoid projections into the vessel lumen or polypoid tumor thrombi covered by endothelial layer)
  8. Adrenal sinusoid invasion (sinusoid is endothelial lined vessel in adrenal gland with little supportive tissue; consider only sinusoids within tumor)
  9. Capsular invasion (nests or cords of tumor extending into or through capsule with a stromal reaction); either incomplete or complete)

Modified Weiss criteria (score of 3 or more suggests malignancy):

Adults
Volante criteria

Simplified criteria by Volante et al (not widely used) is as follows:

Wieneke et al and Dehner & Hill

Wieneke et al and Dehner & Hill proposed the following very simple system:

Pediatrics
Micrograph of an adrenocortical carcinoma (left of image - dark blue) and the adrenal cortex it arose from (right-top of image - pink/light blue). Benign adrenal medulla is present (right-middle of image - gray/blue). H&E stain. - Source: https://librepathology.org
Micrograph of pheochromocytoma. Source: By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=5938524
Histopathology of adrenal pheochromocytoma. Adrenectomy specimen. Source: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=535945
Micrograph of pheochromocytoma. Source: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=535944

Epidemiology and demographics

Risk factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Symptoms in children

Symptoms in adults

Presentation of non-functional adrenal carcinoma

Physical Examination

Laboratory findings

Laboratory findings of different hormonal syndromes in adrenal carcinoma
Hormonal syndrome Laboratory findings
Cushing syndrome
Virilization
Conn syndrome
Feminization

Imaging studies

Imaging studies for the diagnosis of adrenal carcinoma
Imaging study Details
CT[46]
MRI
Bone scan
PET scan[47][48][49][50][51][52]
123I-metaiodobenzylguanidine SPECT[50]
Molecular imaging[53]
Adrenal angiography
Adrenal venography
Ultrasound exam

Biopsy

Adrenalectomy

Treatment

Medical Therapy

Different types of medical therapies for treatment of adrenal carcinoma
Type of medical therapy Details
Radiation therapy There are following two types of radiation therapies that can be used for the treatment of adrenal carcinoma:
Radiofrequency ablation
Chemotherapy (chemoembolization)[55][56][57][58]
Hormonal therapy
Biological therapy (immunotherapy)
Targeted therapy
mTOR antagonists

Surgery

5-year disease-specific survival rate stratification in relation to the disease stage at the time of ACC tumor resection
Stage of the disease at the time of tumor resection 5-year disease-specific survival
Stage I 82%
Stage II 58%
Stage III 55%
Stage IV 18%
Comparison of UICC and ENSAT staging systems for adrenocortical carcinoma
Stage UICC/WHO 2004 ENSAT 2008
I
  • T1, N0, M0
  • T1, N0, M0
II
  • T2, N0, M0
  • T2, N0, M0
III
  • T1-2, N1, M0
  • T3, N0, M0
  • T1-2, N1, M0
  • T3-4, N0-1, M0
IV
  • T1–4, N0-1, M1
  • T3, N1, M0
  • T4, N0-1, M0
  • T1–4, N0-1, M1

T1: tumor  5 cm; T2: tumor  5 cm; T3: tumor infiltration in surrounding tissue; T4: tumor infiltration in adjacent organs [ENSAT additionally the presence of a tumor thrombus in the Vena Cava or Vena Renalis]; N0: absence of positive lymph nodes; N1: presence of positive lymph nodes; M0: absence of distant metastases; M1: presence of distant metastasis.

Differentiating Adrenal carcinoma from other Diseases

Bilateral

Unilateral

References

  1. 1.0 1.1 Lam AK (2017). "Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours". Endocr Pathol. 28 (3): 213–227. doi:10.1007/s12022-017-9484-5. PMID 28477311.
  2. "Adrenocortical Carcinoma Treatment - National Cancer Institute".
  3. "WHO Classification of Tumours of Endocrine Organs. Fourth Edition - WHO - OMS -".
  4. "Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours - Semantic Scholar".
  5. 5.0 5.1 Pinto EM, Chen X, Easton J, Finkelstein D, Liu Z, Pounds S; et al. (2015). "Genomic landscape of paediatric adrenocortical tumours". Nat Commun. 6: 6302. doi:10.1038/ncomms7302. PMC 4352712. PMID 25743702.
  6. Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA; et al. (2016). "Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma". Cancer Cell. 30 (2): 363. doi:10.1016/j.ccell.2016.07.013. PMID 27505681.
  7. Zheng S, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA; et al. (2016). "Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma". Cancer Cell. 29 (5): 723–736. doi:10.1016/j.ccell.2016.04.002. PMC 4864952. PMID 27165744.
  8. Assié G, Letouzé E, Fassnacht M, Jouinot A, Luscap W, Barreau O; et al. (2014). "Integrated genomic characterization of adrenocortical carcinoma". Nat Genet. 46 (6): 607–12. doi:10.1038/ng.2953. PMID 24747642.
  9. 9.0 9.1 Weiss LM (1984). "Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors". Am J Surg Pathol. 8 (3): 163–9. PMID 6703192.
  10. "Mechanism of abnormal production of adrenal androgens in patients with adrenocortical adenomas and carcinomas | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
  11. "Variable Expression of the Transcription Factors cAMP Response Element-Binding Protein and Inducible cAMP Early Repressor in the Normal Adrenal Cortex and in Adrenocortical Adenomas and Carcinomas | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
  12. Fassnacht M, Libé R, Kroiss M, Allolio B (2011). "Adrenocortical carcinoma: a clinician's update". Nat Rev Endocrinol. 7 (6): 323–35. doi:10.1038/nrendo.2010.235. PMID 21386792.
  13. Menon V, Krishnamurthy SV (2006). "Adrenocortical carcinomas: a 12-year clinicopathologic study of 15 cases". Indian J Pathol Microbiol. 49 (1): 7–11. PMID 16625963.
  14. Libè R, Groussin L, Tissier F, Elie C, René-Corail F, Fratticci A; et al. (2007). "Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity". Clin Cancer Res. 13 (3): 844–50. doi:10.1158/1078-0432.CCR-06-2085. PMID 17289876.
  15. McCabe MJ, Pinese M, Chan CL, Sheriff N, Thompson TJ, Grady J; et al. (2019). "Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases". Cold Spring Harb Mol Case Stud. 5 (2). doi:10.1101/mcs.a003764. PMC 6549567 Check |pmc= value (help). PMID 30936196.
  16. Magro G, Esposito G, Cecchetto G, Dall'Igna P, Marcato R, Gambini C; et al. (2012). "Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical expression of matrix metalloproteinase type 2 and human leucocyte-associated antigen (HLA) class II antigens. Results from the Italian Pediatric Rare Tumor (TREP) Study project". Hum Pathol. 43 (1): 31–9. doi:10.1016/j.humpath.2011.04.016. PMID 21820153.
  17. Tischler AS, Kimura N, Mcnicol AM (2006). "Pathology of pheochromocytoma and extra-adrenal paraganglioma". Ann N Y Acad Sci. 1073: 557–70. doi:10.1196/annals.1353.059. PMID 17102124.
  18. Ragazzon B, Libé R, Gaujoux S, Assié G, Fratticci A, Launay P; et al. (2010). "Transcriptome analysis reveals that p53 and {beta}-catenin alterations occur in a group of aggressive adrenocortical cancers". Cancer Res. 70 (21): 8276–81. doi:10.1158/0008-5472.CAN-10-2014. PMID 20959480.
  19. Ragazzon B, Libé R, Assié G, Tissier F, Barreau O, Houdayer C; et al. (2014). "Mass-array screening of frequent mutations in cancers reveals RB1 alterations in aggressive adrenocortical carcinomas". Eur J Endocrinol. 170 (3): 385–91. doi:10.1530/EJE-13-0778. PMID 24347427.
  20. Tissier F (2008). "[Sporadic adrenocortical tumors: genetics and perspectives for the pathologist]". Ann Pathol. 28 (5): 409–16. doi:10.1016/j.annpat.2008.07.005. PMID 19068395.
  21. Gicquel C, Bertagna X, Gaston V, Coste J, Louvel A, Baudin E; et al. (2001). "Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors". Cancer Res. 61 (18): 6762–7. PMID 11559548.
  22. Das S, Sengupta M, Islam N, Roy P, Datta C, Mishra PK; et al. (2016). "Weineke criteria, Ki-67 index and p53 status to study pediatric adrenocortical tumors: Is there a correlation?". J Pediatr Surg. 51 (11): 1795–1800. doi:10.1016/j.jpedsurg.2016.07.014. PMID 27567308.
  23. Chatterjee G, DasGupta S, Mukherjee G, Sengupta M, Roy P, Arun I; et al. (2015). "Usefulness of Wieneke criteria in assessing morphologic characteristics of adrenocortical tumors in children". Pediatr Surg Int. 31 (6): 563–71. doi:10.1007/s00383-015-3708-x. PMID 25895073.
  24. "Adrenal Carcinoma: Practice Essentials, Background, Pathophysiology".
  25. "Adrenal Cancer Causes and Symptoms".
  26. 26.0 26.1 Libè R, Fratticci A, Bertherat J (2007). "Adrenocortical cancer: pathophysiology and clinical management". Endocr Relat Cancer. 14 (1): 13–28. doi:10.1677/erc.1.01130. PMID 17395972.
  27. 27.0 27.1 Cabezon-Gutierrez L, Franco-Moreno AI, Khosravi-Shahi P, Custodio-Cabello S, Garcia-Navarro MJ, Martin-Diaz RM (2015). "Clinical Case of Metastatic Adrenocortical Carcinoma With Unusual Evolution: Review the Literature". World J Oncol. 6 (6): 485–490. doi:10.14740/wjon936w. PMC 5624676. PMID 28983351.
  28. Hsing AW, Nam JM, Co Chien HT, McLaughlin JK, Fraumeni JF (1996). "Risk factors for adrenal cancer: an exploratory study". Int J Cancer. 65 (4): 432–6. doi:10.1002/(SICI)1097-0215(19960208)65:4<432::AID-IJC6>3.0.CO;2-Y. PMID 8621222.
  29. "Adrenal Gland Cancer (Adrenocortical Carcinoma) | Cleveland Clinic: Health Library".
  30. "Top Adrenal Cancer Causes & Factors That Put You at Risk | CTCA".
  31. "Adrenal Cancer Risk Factors".
  32. "Adrenal Cancer Risk Factors | Roswell Park Comprehensive Cancer Center".
  33. "Adrenal Cancer: Causes, Symptoms, and Diagnosis".
  34. "Adrenal cancer - Symptoms and causes - Mayo Clinic".
  35. 35.0 35.1 Weiss LM, Medeiros LJ, Vickery AL (1989). "Pathologic features of prognostic significance in adrenocortical carcinoma". Am J Surg Pathol. 13 (3): 202–6. PMID 2919718.
  36. Moreno S, Montoya G, Armstrong J, Leteurtre E, Aubert S, Vantyghem MC; et al. (2004). "Profile and outcome of pure androgen-secreting adrenal tumors in women: experience of 21 cases". Surgery. 136 (6): 1192–8. doi:10.1016/j.surg.2004.06.046. PMID 15657575.
  37. Wagner M, Walter PR, Ghnassia JP, Gasser B (1993). "[Adrenocortical tumors. I. Prognostic evaluation of a series of 17 cases using the Weiss criteria]". Ann Pathol. 13 (5): 306–11. PMID 8311856.
  38. Gandour MJ, Grizzle WE (1986). "A small adrenocortical carcinoma with aggressive behavior. An evaluation of criteria for malignancy". Arch Pathol Lab Med. 110 (11): 1076–9. PMID 3778125.
  39. Jain M, Kapoor S, Mishra A, Gupta S, Agarwal A (2010). "Weiss criteria in large adrenocortical tumors: a validation study". Indian J Pathol Microbiol. 53 (2): 222–6. doi:10.4103/0377-4929.64325. PMID 20551521.
  40. "Hypoaldosteronism accompanied by normal or elevated mineralocorticosteroid pathway steroid: a marker of adrenal carcinoma. | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
  41. "ADRENAL CORTICAL CARCINOMA IN A MALE WITH EXCESS GONADOTROPIN IN THE URINE | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic".
  42. "UpToDate".
  43. Allolio B, Fassnacht M (2006). "Clinical review: Adrenocortical carcinoma: clinical update". J Clin Endocrinol Metab. 91 (6): 2027–37. doi:10.1210/jc.2005-2639. PMID 16551738.
  44. Sandrini R, Ribeiro RC, DeLacerda L (1997). "Childhood adrenocortical tumors". J Clin Endocrinol Metab. 82 (7): 2027–31. doi:10.1210/jcem.82.7.4057. PMID 9215267.
  45. Moreno S, Guillermo M, Decoulx M, Dewailly D, Bresson R, Proye Ch (2006). "Feminizing adreno-cortical carcinomas in male adults. A dire prognosis. Three cases in a series of 801 adrenalectomies and review of the literature". Ann Endocrinol (Paris). 67 (1): 32–8. PMID 16596055.
  46. Szolar DH, Korobkin M, Reittner P, Berghold A, Bauernhofer T, Trummer H; et al. (2005). "Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT". Radiology. 234 (2): 479–85. doi:10.1148/radiol.2342031876. PMID 15671003.
  47. Groussin L, Bonardel G, Silvéra S, Tissier F, Coste J, Abiven G; et al. (2009). "18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of adrenocortical tumors: a prospective study in 77 operated patients". J Clin Endocrinol Metab. 94 (5): 1713–22. doi:10.1210/jc.2008-2302. PMID 19190108.
  48. Khan TS, Sundin A, Juhlin C, Långström B, Bergström M, Eriksson B (2003). "11C-metomidate PET imaging of adrenocortical cancer". Eur J Nucl Med Mol Imaging. 30 (3): 403–10. doi:10.1007/s00259-002-1025-9. PMID 12634969.
  49. Dong, Aisheng; Cui, Yong; Wang, Yang; Zuo, Changjing; Bai, Yushu (2014). "18F-FDG PET/CT of Adrenal Lesions". American Journal of Roentgenology. 203 (2): 245–252. doi:10.2214/AJR.13.11793. ISSN 0361-803X.
  50. 50.0 50.1 Shulkin BL, Thompson NW, Shapiro B, Francis IR, Sisson JC (1999). "Pheochromocytomas: imaging with 2-[fluorine-18]fluoro-2-deoxy-D-glucose PET". Radiology. 212 (1): 35–41. doi:10.1148/radiology.212.1.r99jl3035. PMID 10405717.
  51. Ansquer C, Scigliano S, Mirallié E, Taïeb D, Brunaud L, Sebag F; et al. (2010). "18F-FDG PET/CT in the characterization and surgical decision concerning adrenal masses: a prospective multicentre evaluation". Eur J Nucl Med Mol Imaging. 37 (9): 1669–78. doi:10.1007/s00259-010-1471-8. PMID 20490488.
  52. Blake MA, Slattery JM, Kalra MK, Halpern EF, Fischman AJ, Mueller PR; et al. (2006). "Adrenal lesions: characterization with fused PET/CT image in patients with proved or suspected malignancy--initial experience". Radiology. 238 (3): 970–7. doi:10.1148/radiol.2383042164. PMID 16505394.
  53. Hahner S, Stuermer A, Kreissl M, Reiners C, Fassnacht M, Haenscheid H; et al. (2008). "[123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes". J Clin Endocrinol Metab. 93 (6): 2358–65. doi:10.1210/jc.2008-0050. PMID 18397978.
  54. "Adrenocortical Carcinoma Treatment (PDQ®)–Patient Version - National Cancer Institute".
  55. Kwok GTY, Zhao JT, Glover AR, Gill AJ, Clifton-Bligh R, Robinson BG; et al. (2019). "microRNA-431 as a Chemosensitizer and Potentiator of Drug Activity in Adrenocortical Carcinoma". Oncologist. 24 (6): e241–e250. doi:10.1634/theoncologist.2018-0849. PMC 6656493 Check |pmc= value (help). PMID 30918109.
  56. Abraham J, Bakke S, Rutt A, Meadows B, Merino M, Alexander R; et al. (2002). "A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist". Cancer. 94 (9): 2333–43. doi:10.1002/cncr.10487. PMID 12015757.
  57. Berruti A, Terzolo M, Pia A, Angeli A, Dogliotti L (1998). "Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma. Italian Group for the Study of Adrenal Cancer". Cancer. 83 (10): 2194–200. PMID 9827725.
  58. Williamson SK, Lew D, Miller GJ, Balcerzak SP, Baker LH, Crawford ED (2000). "Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma: a Southwest Oncology Group Study". Cancer. 88 (5): 1159–65. PMID 10699907.





Linked-in.jpg